Clinical effects of nanocrystalline hydroxyapatite paste in the treatment of intrabony periodontal defects: a randomized controlled clinical study

The purpose of the present randomized controlled clinical study was to compare the clinical outcomes of papilla preservation flap surgery with or without the application of a novel nanocrystalline hydroxyapatite (nano-HA) bone graft substitute. Fourteen patients with paired intrabony periodontal defects of ≥4 mm participated in this split-mouth design study. The defects in each subject were randomly selected to receive nano-HA paste in conjunction with papilla preservation flaps or papilla preservation flaps alone. Probing bone levels (PBL) from a customized acrylic stent and probing pocket depths (PPD) were measured at baseline and again 6 months following surgery. No differences in any of the investigated parameters were observed at baseline between the two groups. Healing was uneventful in all patients. Both treatments resulted in significant improvements between baseline and 6 months (p < 0.05). At 6 months after therapy, the sites treated with nano-HA paste showed a reduction in mean PPD from 8.3 ± 1.2 to 4.0 ± 1.1 mm and a gain in PBL of 4.3 ± 1.4 mm, whereas in the control group, the mean PPD changed from 7.9 ± 1.2 mm to 5.0 ± 1.2 mm and PBL gain was 2.6 ± 1.4 mm. Results demonstrated statistically greater PPD reduction and PBL gain (p < 0.05) in the test group as compared with the control group. In conclusion, after 6 months, the treatment of intrabony periodontal defects with a nano-HA paste leads to significantly improved clinical outcomes when compared with papilla preservation flap surgery alone.     

Comparison of prognostic usefulness (three years) of computed tomographic angiography versus 64-slice computed tomographic calcium scanner in subjects without significant coronary artery disease

Coronary computerized tomographic angiography (CTA) has been used as a noninvasive method for ruling out high-grade stenoses. Even in the absence of such stenoses, analysis of coronary atherosclerosis may provide for important prognostic information, and this may be superior to exclusive coronary artery calcium scoring. We tested this hypothesis in patients undergoing CTA for clinical indications who had no stenoses requiring revascularization. From December 2004 to December 2006, 706 consecutive patients who underwent CTA but had no high-grade stenoses were included (58% men, mean age 59 ± 11 years). CTA and coronary artery calcium scoring (Agatston method) were performed using a 64-slice CT scanner with a gantry rotation time of 330 ms. CT angiograms were categorized as completely normal (group 1), showing minor plaque (group 2), or showing intermediate stenoses (group 3). Follow-up information was obtained in 670 patients (95%) over a mean of 3.2 years. There were 31 major adverse events (5%), namely 9 deaths (all noncoronary), 2 myocardial infarctions, 5 strokes, 13 coronary revascularization procedures (percutaneous or surgical > 6 months after CTA), and 2 peripheral percutaneous interventions. Coronary status as defined by CTA was predictive of major events after adjustment for age and gender. In group 1, the probability of event-free survival at 3 years was 100%; in group 2, it was 96%; and in group 3, it was 91%. Compared to group 1, the risk in group 2 was increased 2.3-fold, and in group 3, it was increased 5.6-fold after adjusting for age and gender. However, after addition of the coronary artery calcium score to the regression analysis, CT angiographic status no longer appeared to be predictive. In conclusion, the risk of a major adverse cardiovascular event or death increased in a graded manner with degree of coronary atherosclerosis as defined by CTA even in the absence of high-grade coronary stenoses. However, in the absence of high-grade stenoses, we were unable to demonstrate a superior prognostic value of CTA compared to coronary artery calcium.     

Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis

Reduced functional bladder capacity and concomitant increased micturition frequency (pollakisuria) are common lower urinary tract symptoms associated with conditions such as cystitis, prostatic hyperplasia, neurological disease, and overactive bladder syndrome. These symptoms can profoundly affect the quality of life of afflicted individuals, but available pharmacological treatments are often unsatisfactory. Recent work has demonstrated that the cation channel TRPV4 is highly expressed in urothelial cells and plays a role in sensing the normal filling state of the bladder. In this article, we show that the development of cystitis-induced bladder dysfunction is strongly impaired in Trpv4(-/-) mice. Moreover, we describe HC-067047, a previously uncharacterized, potent, and selective TRPV4 antagonist that increases functional bladder capacity and reduces micturition frequency in WT mice and rats with cystitis. HC-067047 did not affect bladder function in Trpv4(-/-) mice, demonstrating that its in vivo effects are on target. These results indicate that TRPV4 antagonists may provide a promising means of treating bladder dysfunction.     

DNA polymerase θ up-regulation is associated with poor survival in breast cancer,perturbs DNA replication,and promotes genetic instability

“Replicative stress” is one of the main factors underlying neoplasia from its early stages. Genes involved in DNA synthesis may therefore represent an underexplored source of potential prognostic markers for cancer. To this aim, we generated gene expression profiles from two independent cohorts (France, n = 206; United Kingdom, n = 117) of patients with previously untreated primary breast cancers. We report here that among the 13 human nuclear DNA polymerase genes, DNA Polymerase θ (POLQ) is the only one significantly up-regulated in breast cancer compared with normal breast tissues. Importantly, POLQ up-regulation significantly correlates with poor clinical outcome (4.3-fold increased risk of death in patients with high POLQ expression), and this correlation is independent of Cyclin E expression or the number of positive nodes, which are currently considered as markers for poor outcome. POLQ expression provides thus an additional indicator for the survival outcome of patients with high Cyclin E tumor expression or high number of positive lymph nodes. Furthermore, to decipher the molecular consequences of POLQ up-regulation in breast cancer, we generated human MRC5-SV cell lines that stably overexpress POLQ. Strong POLQ expression was directly associated with defective DNA replication fork progression and chromosomal damage. Therefore, POLQ overexpression may be a promising genetic instability and prognostic marker for breast cancer.     

Occupational exposure to polycyclic aromatic hydrocarbons and DNA damage by industry: a nationwide study in Germany

Exposure to polycyclic aromatic hydrocarbons (PAH) and DNA damage were analyzed in coke oven (n = 37), refractory (n = 96), graphite electrode (n = 26), and converter workers (n = 12), whereas construction workers (n = 48) served as referents. PAH exposure was assessed by personal air sampling during shift and biological monitoring in urine post shift (1-hydroxypyrene, 1-OHP and 1-, 2 + 9-, 3-, 4-hydroxyphenanthrenes, ΣOHPHE). DNA damage was measured by 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) and DNA strand breaks in blood post shift. Median 1-OHP and ΣOHPHE were highest in converter workers (13.5 and 37.2 μg/g crea). The industrial setting contributed to the metabolite concentrations rather than the air-borne concentration alone. Other routes of uptake, probably dermal, influenced associations between air-borne concentrations and levels of PAH metabolites in urine making biomonitoring results preferred parameters to assess exposure to PAH. DNA damage in terms of 8-oxo-dGuo and DNA strand breaks was higher in exposed workers compared to referents ranking highest for graphite-electrode production. The type of industry contributed to genotoxic DNA damage and DNA damage was not unequivocally associated to PAH on the individual level most likely due to potential contributions of co-exposures.     

Interspecies difference in liver-specific functions and biotransformation of testosterone of primary rat,porcine and human hepatocyte in an organotypical sandwich culture

Interspecies difference is an important issue in toxicology research. We compared the potential in vitro metabolism of human, porcine and rat hepatocytes over 2 weeks in culture in an organotypical culture model which reflects the in vivo situation. All three species show similar LDH-rates. Albumin measurements showed that rat cells are about twice as active as human and porcine hepatocytes. The ethoxyresorufin-O-deethylase (EROD) activity of the rat hepatocytes is with about 14 μU/10⁶ cells distinctly higher than those of porcine and human cells (1.8 and 0.5 μU/10⁶ cells respectively), furthermore, the activity of the rat EROD increases slightly during the prolonged time in culture, whereas those of porcine and human enzymes slightly decrease. Concerning ethoxycoumarin-O-deethylase (ECOD), the enzyme activities are found to be in three different ranges where rat cells show the highest activity with 66 μU/10⁶ cells, porcine hepatocytes exhibit an activity of about 23 μU/10⁶ cells, and human activity is lowest with 0.7 μU/10⁶ cells. All three species show a similar decreasing trend of ECOD during the period of study. Regarding the biotransformation of testosterone, human and porcine liver cells form three major metabolites whereas rat cells form a mixture of all measured metabolites. Hence, in vitro metabolism using porcine hepatocytes would be much more scientific sense than one using rat hepatocytes since the metabolic pathways are much closer to human metabolism.     

Validation and standardization of the Generalized Anxiety Disorder Screener (GAD-7) in the general population

BACKGROUND: The 7-item Generalized Anxiety Disorder Scale (GAD-7) is a practical self-report anxiety questionnaire that proved valid in primary care. However, the GAD-7 was not yet validated in the general population and thus far, normative data are not available. OBJECTIVES: To investigate reliability, construct validity, and factorial validity of the GAD-7 in the general population and to generate normative data. RESEARCH DESIGN: Nationally representative face-to-face household survey conducted in Germany between May 5 and June 8, 2006. SUBJECTS: Five thousand thirty subjects (53.6% female) with a mean age (SD) of 48.4 (18.0) years. MEASURES: The survey questionnaire included the GAD-7, the 2-item depression module from the Patient Health Questionnaire (PHQ-2), the Rosenberg Self-Esteem Scale, and demographic characteristics. RESULTS: Confirmatory factor analyses substantiated the 1-dimensional structure of the GAD-7 and its factorial invariance for gender and age. Internal consistency was identical across all subgroups (alpha = 0.89). Intercorrelations with the PHQ-2 and the Rosenberg Self-Esteem Scale were r = 0.64 (P < 0.001) and r = -0.43 (P < 0.001), respectively. As expected, women had significantly higher mean (SD) GAD-7 anxiety scores compared with men [3.2 (3.5) vs. 2.7 (3.2); P < 0.001]. Normative data for the GAD-7 were generated for both genders and different age levels. Approximately 5% of subjects had GAD-7 scores of 10 or greater, and 1% had GAD-7 scores of 15 or greater. CONCLUSIONS: Evidence supports reliability and validity of the GAD-7 as a measure of anxiety in the general population. The normative data provided in this study can be used to compare a subject's GAD-7 score with those determined from a general population reference group.